Viagra: Curse or blessing for divers?

Appeared in DIVER September 2016

Divers in their 40s, 50s, and 60s who take medication for erectile disfunction need to be aware that if they do so before diving, it's very likely to increase the risk of decompression illness, says CAREN LIEBSCHER. When taken after diving, on the other hand, the drug may be a remedy...

WHEN RESEARCHERS DECIDEto treat rodents with drugs and send them diving in a hyperbaric chamber, scuba-divers will realise that the intention is to find a remedy for decompression illness (DCI). However, such a study will surely attract wider attention when the drug in question is Viagra, one of the best-known names in pharmaceuticals.Less well-known, however, is Viagra’s active substance, sildenafil, which was originally tested as a drug for lowering hypertension. Its beneficial effect for the male part of humanity was more or less a side-effect, and it was this that went on to be extensively marketed by Pfizer and to change so many lives.Nowadays, sildenafil is licensed to treat pulmonary hypertension (raised blood pressure affecting heart and lungs) and other vascular diseases. In an off-label use, it has been used successfully to treat swimming-induced pulmonary edema (SIPE) in triathletes. The main difference from Viagra is that it is administered in lower doses.Sildenafil acts on the endothelium, the inner layer of blood vessels. It dilates these by increasing the vasodilator effect on smooth muscle relaxation, and does this by inhibiting an enzyme, phosphodiesterase type 5 (PDE5). It lowers blood pressure by dilating vessels. Because this effect is similar to that which nitric oxide (NO) has on blood vessels, scientists thought that a vasodilator such as sildenafil could protect against DCI in divers. DCI develops from bubbles that form from micronuclei in blood vessels after decompression, and NO-releasing agents were believed to be able to reduce this bubble formation and prevent serious DCI. However, all hopes for a new DCI remedy were destroyed when the scientists investigated the effect of pre-treatment with sildenafil in animals, and found that not only did it not protect against DCI but could even cause harm.

THE RESEARCHTo evaluate the clinical effects, the researchers pre-treated small rodents with 10mg/kg of sildenafil one hour before exposure (the drug’s effects normally last 2-5 hours). Then the rodents underwent a simulated dive to 90m for 45 minutes in a hyperbaric chamber before staged decompression. Half an hour after the dive, neurological DCI symptoms, blood-cell count and quantification of the level of circulating bubbles in the right cavities were clinically assessed. The control group was not pre-treated with sildenafil but received the same volume of water before a dive of equal conditions. The outcome was negative - there were more cases of DCI in the sildenafil group than in the untreated control group. Further, there were reduced platelet counts in the sildenafil group, a biomarker for decompression stress. In cases of DCI, gas bubbles damage the vascular endothelium and provoke an inflammatory response, activating leukocytes that transmigrate through the endothelium, which explains the reduction in platelet counts.

THE RESULTSDisappointing as these findings were in regard to DCI, they should not be mixed up with the beneficial effects sildenafil has on SIPE in triathletes, effectively mitigating symptoms when taken before starting the activity. Swimming is a totally different activity to scuba-diving, with its depths and pressures, and what’s good for a swimmer can be bad for a diver.The researchers explained that the increased risk of DCI when taking sildenafil before diving was caused by the drug’s vasodilator effect in the central nervous system causing a higher blood flow in the brain and a higher load of considerably more inert gas during hyperbaric exposure, which may then generate bubbling and severe DCI in neurological tissue.Sildenafil and nitric oxide are both powerful vasodilators. In preconditioning studies, NO has proved effective in reducing DCI risk, though this is not simply down to the use of a vasodilator alone.An endogenous (internally originated) NO donor is released as a consequence of exercise, while an exogenous (externally originated) NO donor can be taken in as food. In the study, sildenafil couldn’t reduce bubble formation in an animal, but NO is known to do this in both rodents and humans, as was demonstrated in preconditioning studies. So NO donors must involve properties and mechanisms different from those encountered with sildenafil. This suggests that the presence of gas nuclei attached to the vessel wall is not directly influenced by the vasodilator effect related to elaxation of the smooth muscle. NO seems to have specific effects that are involved in reducing the number of gas nuclei adhering to the surface of the endothelium. It can also trigger important physiological effects such as scavenging superoxide radicals, inhibiting platelet aggregation, modulating endothelial layer permeability and attenuating leukocyte function. Sildenafil does not seem to have these specific effects.

THE POSITIVE SIDEHowever, what may not help in one situation can be beneficial in another. When sildenafil is used 24 hours after the onset of a stroke it has been shown to be beneficial, elevating cerebral blood flow and improving functional recovery of ischemic tissue.This gives new hope that sildenafil could be useful as a supportive treatment of ischemic neurological DCI in divers who have not recovered after initial treatment with hyperbaric oxygen.Preconditioning methods before diving, such as a sauna or light exercise, are beneficial. They trigger the release of endogenous NO, which scavenges micronuclei from the inner layer of blood vessels and so is likely to reduce the risk of DCI.However, heavy exercise or a sauna within 24-48 hours after diving boosts the risk of DCI, because it increases blood flow in most tissues and leads to increased bubble formation from off-gassing nitrogen.In rodents, sildenafil increased the risk of DCI when taken before diving, but we have no knowledge of actual cases among human divers.If a diver has already been hit by neurological DCI and treated in a hyperbaric chamber, sildenafil may help to alleviate the symptoms by increasing cerebral blood flow, but this is an assumption based on stroke studies in rodents and requires more research.

CONCLUSIONThe researchers of this study conclude that pre-treatment with Viagra or other PDE-5-inhibitors promotes the onset and severity of DCI, and this important finding needs to be spread among the diving community.When divers take any drugs, they should first consult their (diving) doctor, and this is especially true of Viagra. Possible interactions with other drugs and interference with underlying diseases in a diving environment should always be discussed and clarified upfront.Further studies on oxidative stress markers in the central nervous system are needed to better understand the underlying mechanisms of sildenafil in DCI. Find out more about the research at www.ncbi.nlm.nih.gov/pubmed/ 23580342

ASK DAN’S EXPERTS

Can people with cochlear implants scuba-dive?

Scuba-diving is a sport with some inherent risk and people with deafness or who have undergone ear surgery may be at increased risk. Regarding return to diving after implantation, a recipient should wait a minimum of three months, be able to auto-inflate (or equalise) the operated ear, be completely healed, be free of symptoms such as vertigo, imbalance and pain, and have complete resolution of the post-operative hemotympanum (blood behind the eardrum). On examination with a microscope, the fistula test should be negative and the tympanic membrane (TM) should not contact the electrode on maximum medial excursion. Your doctor will gently puff air into your ear canal to see if it makes you dizzy or if the eardrum touches the cochlear-implant electrode. Your neurological examination should be normal. Make sure to discuss these recommendations with your otologist and be sure to follow his or her recommendations.

MEDICAL VIEWDAN Europe is a not-for-profit worldwide organisation that provides emergency medical advice and assistance for underwater diving injuries. It also promotes diving safety through research, education, products and services